The physiology and pharmacology of aqueous humor production and intraocular pressure are being studied by the use of an enucleated, arterially perfused eye. Although it is generally assumed that all drugs applied to the cornea exert their effect on intraocular receptors, data obtained during current studies suggest a reevaluation of these concepts may be in order. We have found that when PGE2 is administered in the arterial circulation, no direct effect on the eye is apparent. However, the topical application of PGE2 causes a marked increase in the rate of aqueous humor formation and of IOP. A more provocative indication for the involvement of corneal receptors is the ability of cold air applied to the cornea to cause a lowering of both functions. The mechanism by which timolol causes a lowering of IOP in humans is still an enigma. We have found that timolol is a competent beta-adrenergic blocking agent in the enucleated eye. Yet, though we have no difficulty in demonstrating this type of activity, we are still unable to demonstrate an ocular hypotensive action in this eye preparation.